It is proposed to investigate the structural features of human Cls, the esterase enzyme which constitutes one third of the macromolecular complex, Cl, the first component of serum complement. Procedures to be used in this study include molecular weight analyses, carboxy-terminal and amino-terminal amino acid analysis of the protein, overall amino acid analysis, and determination of individual amino acids and peptide segments involved in the function of the esteratic site. The latter information will be obtained using the technique of affinity labeling, by which a reagent is specifically and covalently bound to some portion of the active site. Finally, it is hoped to characterize Cls isolated from individual isolated serum and gut tissue samples. The Cls in such samples will be isolated and purified by affinity chromatography, a purification procedure which results in almost theoretical yields of the Cls enzyme from serum. The information gained from these studies will be useful in terms of developing new methods for the investigation of the function and structure of other complement proteins, in providing insights into possible mechanisms by which the complement proteins generate specificity for each other, and in understanding the way in which the complement system participates in host defense mechanisms. BIBLIOGRAPHIC REFERENCES: Smith, C.W., Hollers, J.C., Bing, D.H. and Patrick, R.A. (1975): Effects of human Cl inhibitor on complement mediated human leukocyte chemotaxis. J. Immunol. 114, 216-220. Roman, D. P., Jr., Bing, D.H. and Cory, M. (1975): Benzamidine inhibitors of Cls, a subunit of the first component of complement: correlation of partition coefficients with inhibition constants. Fed. Proc. 34, 1777.